1. Field of the Invention
This invention relates to a method and an apparatus that detect organism-originated substances by using an array chip that is employed in deoxyribonucleic acid (DNA) analysis and immunological analysis.
2. Description of the Related Art
In recent years, techniques in the field of generic engineering have rapidly developed, and the human genome project in which one of the objects is to interpret as many as 100,000 base sequences of the human genome has been developed.
On the other hand, an enzyme immunoassay method, a fluorescent antibody method and the like taking advantage of an antigen-antibody reaction have been utilized in diagnoses and research, and techniques of searching for DNA having influence on various genetic diseases have also advanced. As one of the methods, attention has been paid to an array technique.
In this array technique, an array chip (also called a DNA chip), such as the one shown in FIG. 1, is employed as an array chip 1. In the array chip 1, a large number of known complementary DNAs (an example of a specific binding substance) differing from one another, which have already been interpreted, are disposed with high density in matrix form on a carrier 2 such as a membrane filter, a slide glass and the like. For instance, DNA (an example of an organism-originated substance) originated from the cell of healthy subject A is labeled with a labeling substance consisting of a fluorescent dye or a radioactive isotope, and similarly, DNA originated from the cell of subject B having a genetic disease is labeled with the labeling substance. The labeled DNAs of the subjects A, B are dropped on separate array chips and are hybridized with the complementary cDNAs on the separate array chips. Each hybridized cDNA on each array chip is scanned by laser light that excites each labeling substance, and the fluorescent light or radiation emitted from each cDNA is detected by a photo or radiation detector. Next, a labeled signal representing this result of detection, corresponding to the light-emitting position (spot position) on the array chip, is obtained, and based on this labeled signal, it is judged which cDNA has been hybridized by the cDNA of each subject. The ratio or difference of the labeled signals obtained between both subjects is calculated, and between both subjects, the hybridized cDNAs are compared. In this way, the gene manifested or lost due to the above-mentioned disease (hereinafter referred to as change in manifestation) is specified. Note that if two images represented by the labeled signals are printed or output to a monitor, the change in manifestation can be visually recognized and specified. On the other hand, the ratio between the labeled signals that are obtained from both subjects becomes greater (or smaller) at a position where the change in manifestation exists. Therefore, in the order that the ratio of the labeled signals between both subjects is greater (or smaller), the signal value ratios at 50 spot positions, for example, are caused to correspond to the positions at which the labeled signals were obtained, and these corresponding relations are output as a measurement-result table representing measurement results. Based on this measurement-result table and images displayed on a monitor, the positions at which the labeled signals were obtained are calculated, whereby the change in manifestation can be specified.
The signal value corresponding to each spot position is obtained by setting a template, on which circular ROIs (regions of interest) are disposed at positions corresponding to the spot positions, onto images represented by the labeled signals and detecting a signal value at a position corresponding to the position of the ROI on this template.
However, the above-mentioned method of disposing spot positions on the array chip varies depending on manufacturers of array chips and test purposes. For this reason, if other array chips are employed, in the case where a template is used only for array chips made by a specific manufacturer or for a specific test purpose, the detection of signal values cannot be performed because the spot positions on the array chip do not correspond to the ROI positions on the template. In such a case, if a new template, on which ROIs are disposed at positions corresponding to the spot positions on an array chip used, is generated, signal values can be detected. However, an array chip has as few as 500 spot positions or as many as a few tens of thousand spot positions, and the method of disposing spot positions varies from array chip to array chip. Thus, the operation of generating templates is fairly difficult and time consuming.